Recent analysis of the public health risks and benefits of replacing cigarettes with a deep nicotine aerosol inhaler (if one were to exist) suggests that such a replacement would have a favourable impact (Sumner II W “Estimating the health consequences of replacing cigarettes with nicotine inhalers” Tobacco Control 2003;12:124-132). The difficulties arise in developing a device that generates a sufficiently fine aerosol to allow peripheral lung delivery like that of a cigarette in a cost effective and operationally acceptable manner to current smokers, whether or not they intent to quit using nicotine. With currently available nicotine replacement therapy (gum, patch, nasal inhaler, oral vapour inhaler) most attempts at smoking cessation fail, and relapse rates remain over 75%. Many hard core smokers suffer from an underlying psychiatric problem that nicotine may help to ameliorate (Pomerleau CS “Co-factors for smoking and evolutionary psychobiology” Addiction 1997;92:397-408). None of the available nicotine delivery devices listed above mimic a cigarette in terms of the rapid puff-by-puff delivery of an arterial bolus that reaches the brain within seconds, and this may explain why most individuals relapse to cigarette smoking. While smoking, peak arterial plasma nicotine concentration may be 10 times greater than venous concentrations. It is only by absorption through the lungs that the rapid arterial bolus nicotine delivery of a cigarette can be achieved, as opposed to the relatively slower venous delivery via buccal or nasal mucosa or skin, which is characteristic of current nicotine delivery devices including the oral vapour inhaler. The key to efficient arterial (central nervous system) nicotine delivery is the particle size of the nicotine aerosol. Nicotine vapour entering the mouth condenses onto the mucosal surface of the mouth and throat. Large aerosol droplets affect the upper airway as well. Only nicotine carried by fine droplets or particles is available for absorption into the pulmonary circulation and reaches the brain quickly in high concentration. Cigarette smoke particles have a mass median aerodynamic diameter (MMAD) of 0.4 μm. Such small particles deposit mainly in the alveoli of the lung from which they may be rapidly absorbed into the pulmonary circulation.
Recent improvements in the technology of medicinal inhalers for asthma and chronic lung disease has led to the development of solution formulations for pressurised metered-dose inhalers (pMDI's) that can generate fine droplet aerosols, improving upon that of pMDI's using solid particle suspension formulations and dry powder inhaler technology which are inherently limited in their potential to go into the ultra-fine particle size range. Preliminary tests of a hydrofluoroalkane/ethanol/nicotine solution formulation pMDI has shown an MMAD of 1.5 μm (Andrus PG et. al. “Nicotine microaerosol inhaler” 1999 Canadian Respiratory Journal; Vol 6 No 6:509-512), which is sufficiently small to allow cigarette simulating peripheral lung delivery. The hydrofluoroalkane/ethanol solution has also been developed to replace the marijuana cigarette (Davies, R. J. et al. U.S. Patent Application 20050061314 A1, Mar. 24, 2005; and Peart, J. et al. U.S. Patent Application 20040258622 A1, Dec. 23, 2004) for the same reasons as those which apply to nicotine, and in recognition of the many medicinal benefits of cannabinoids (i.e. tetrahydrocannabinol (THC)) in treating chronic pain and nausea. That is, nicotine and cannabis have been historically and are presently used most efficiently and effectively by deep inhalation, and HFA solution formulations allow the simulation of this where other inhaler technologies fall short.
The parameters of smoking (number of puffs per cigarette, number of cigarettes per day) are not random, but have been refined by user behaviour and preference over the long history of cigarette smoking for therapeutic effect. Simulation of this process by clean deep inhaler is the object of the present invention. A further difficulty however in the simulation of smoking by inhaler, which is addressed by the present invention, is the number of puffs that are typically inhaled in the course of a day. As a result of the high efficiency of pulmonary circulation delivery by a deep inhaler or a cigarette, a unit dose of one cigarette equivalent is best delivered by several puffs over several minutes. If the entire unit dose were delivered in one puff by deep inhalation, this would be less enjoyable and potentially dangerously over stimulating to the user. The entire dose could be delivered to the upper airway in one puff, for example the buccal or nasal mucosa, because it would effectively be delivered more slowly as it is more gradually absorbed into the venous circulation. This of course forgoes the advantages and user preferences for deep inhalation as described above. pMDI's for asthma or emphysema are intended to be discharged 4 to 8 times per day giving the inhaler's 200 puffs a life of about a month. Typically a smoker inhales 10 times per cigarette for 20 cigarettes per day thereby using up one inhaler equivalent per day. This rate of inhaler expenditure is undesirable from both a cost and user acceptability standpoint.